{
  "abstract": "Introduction Diabetes is a significant modifiable risk factor for cognitive dysfunction. There are currently no effective treatments that delay or reverse the progression of cognitive dysfunction. Accumulating evidence demonstrates that specific antidiabetes medications hold promise in improving cognitive function. However, the comparative effects of various antidiabetic drug classes on cognitive protection remain to be fully elucidated. This study aims to investigate and compare the cognitive benefits of liraglutide, empagliflozin and linagliptin on achieving mild cognitive impairment (MCI) remission in individuals with type 2 diabetes (T2D).Methods and analysis The LIGHT-MCI trial is an investigator-initiated, multicentre, open-label, parallel-group, randomised, superiority trial involving T2D patients with MCI, consisting of a 48-week core study followed by an extension phase through to 76 weeks. A total of 396 participants will be randomly allocated 1:1:1 to receive liraglutide, empagliflozin or linagliptin treatment. The primary outcome measure is the efficacy difference of liraglutide, empagliflozin and linagliptin in achieving MCI remission in individuals with T2D. The key secondary outcome measures include changes in scores of general cognition and various cognitive subdomains (including processing speed, executive function, immediate memory, visuospatial construction ability, language, attention and delayed memory), basic and instrumental daily living ability, MRI-derived normalised measures of total brain volume, cerebral microstructures, cortical and nuclear volume, white matter hyperintensity, volume, white matter microstructural integrity, odour-induced brain activation and resting-state functional connectivity, olfactory function and metabolic parameters.Ethics and dissemination The LIGHT-MCI trial has received approval from the Ethics Committees of the Drum Tower Hospital Affiliated to Nanjing University Medical School (2022-092-02) and other participating centres in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonisation for Good Clinical Practice (ICH GCP E6). Informed consent is required for participation. Findings from this trial are disseminated through peer-reviewed publications, conference presentations, newsletters and social media.Trial registration number NCT05313529.",
  "authors": [
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Congcong Yu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Huijie Yang"
    },
    {
      "affiliations": [
        "Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Bing Zhang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Shihua Chen"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Sijue Yang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Fangyi Li"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Wenhui Zhu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Beibei Zhai"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Tianyu Wu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Shengyi Zhao"
    },
    {
      "affiliations": [
        "Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Wen Zhang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Xuewei Tong"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Yanjie Duan"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Lu Zhang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Yining Chao"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Jindan Wu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China"
      ],
      "name": "Xiaowei Zhu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Kun Wang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Changzhou No 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China"
      ],
      "name": "Xinhua Ye"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Xiaoya Zhang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China"
      ],
      "name": "Xiang Xu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China"
      ],
      "name": "Haiyan Cheng"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China"
      ],
      "name": "Jie Liu"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Changzhou No 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China"
      ],
      "name": "Jie Zhang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, The Affiliated Changzhou No 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China"
      ],
      "name": "Ying Wang"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Zhou Zhang"
    },
    {
      "affiliations": [
        "Department of Clinical Epidemiology, Children's Hospital of Fudan University National Children’s Medical Center, Shanghai, Shanghai, China"
      ],
      "name": "Weili Yan"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, Jiangsu, China"
      ],
      "name": "Yan Bi"
    }
  ],
  "title": "Evaluating the effects of liraglutide, empagliflozin and linagliptin on mild cognitive impairment remission in patients with type 2 diabetes (LIGHT-MCI): study protocol for a multicentre, randomised controlled trial with an extension phase",
  "uid": "f9d31a52-5b62-56f0-8488-b2a1834b2071"
}